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1.
J Biomed Opt ; 30(Suppl 1): S13702, 2025 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-39034960

RESUMEN

Significance: Near-infrared autofluorescence (NIRAF) utilizes the natural autofluorescence of parathyroid glands (PGs) to improve their identification during thyroid surgeries, reducing the risk of inadvertent removal and subsequent complications such as hypoparathyroidism. This study evaluates NIRAF's effectiveness in real-world surgical settings, highlighting its potential to enhance surgical outcomes and patient safety. Aim: We evaluate the effectiveness of NIRAF in detecting PGs during thyroidectomy and central neck dissection and investigate autofluorescence characteristics in both fresh and paraffin-embedded tissues. Approach: We included 101 patients diagnosed with papillary thyroid cancer who underwent surgeries in 2022 and 2023. We assessed NIRAF's ability to locate PGs, confirmed via parathyroid hormone assays, and involved both junior and senior surgeons. We measured the accuracy, speed, and agreement levels of each method and analyzed autofluorescence persistence and variation over 10 years, alongside the expression of calcium-sensing receptor (CaSR) and vitamin D. Results: NIRAF demonstrated a sensitivity of 89.5% and a negative predictive value of 89.1%. However, its specificity and positive predictive value (PPV) were 61.2% and 62.3%, respectively, which are considered lower. The kappa statistic indicated moderate to substantial agreement (kappa = 0.478; P < 0.001 ). Senior surgeons achieved high specificity (86.2%) and PPV (85.3%), with substantial agreement (kappa = 0.847; P < 0.001 ). In contrast, junior surgeons displayed the lowest kappa statistic among the groups, indicating minimal agreement (kappa = 0.381; P < 0.001 ). Common errors in NIRAF included interference from brown fat and eschar. In addition, paraffin-embedded samples retained stable autofluorescence over 10 years, showing no significant correlation with CaSR and vitamin D levels. Conclusions: NIRAF is useful for PG identification in thyroid and neck surgeries, enhancing efficiency and reducing inadvertent PG removals. The stability of autofluorescence in paraffin samples suggests its long-term viability, with false positives providing insights for further improvements in NIRAF technology.


Asunto(s)
Imagen Óptica , Glándulas Paratiroides , Espectroscopía Infrarroja Corta , Tiroidectomía , Humanos , Glándulas Paratiroides/cirugía , Glándulas Paratiroides/metabolismo , Masculino , Femenino , Persona de Mediana Edad , Imagen Óptica/métodos , Adulto , Espectroscopía Infrarroja Corta/métodos , Adhesión en Parafina/métodos , Anciano , Cáncer Papilar Tiroideo/cirugía , Cáncer Papilar Tiroideo/patología , Cáncer Papilar Tiroideo/metabolismo , Receptores Sensibles al Calcio/metabolismo , Receptores Sensibles al Calcio/análisis
2.
World J Clin Cases ; 12(22): 5151-5158, 2024 Aug 06.
Artículo en Inglés | MEDLINE | ID: mdl-39109014

RESUMEN

BACKGROUND: The common cause of sodium nitrite poisoning has shifted from previous accidental intoxication by exposure or ingestion of contaminated water and food to recent alarming intentional intoxication as an employed method of suicide/exit. The subsequent formation of methemoglobin (MetHb) restricts oxygen transport and utilization in the body, resulting in functional hypoxia at the tissue level. In clinical practice, a mismatch of cyanotic appearance and oxygen partial pressure usually contributes to the identification of methemoglobinemia. Prompt recognition of characteristic mismatch and accurate diagnosis of sodium nitrite poisoning are prerequisites for the implementation of standardized systemic interventions. CASE SUMMARY: A pregnant woman was admitted to the Department of Critical Care Medicine at the First Affiliated Hospital of Harbin Medical University due to consciousness disorders and drowsiness 2 h before admission. Subsequently, she developed vomiting and cyanotic skin. The woman underwent orotracheal intubation, invasive mechanical ventilation (IMV), and correction of internal environment disturbance in the ICU. Her premature infant was born with a higher-than-normal MetHb level of 3.3%, and received detoxification with methylene blue and vitamin C, supplemental vitamin K1, an infusion of fresh frozen plasma, as well as respiratory support via orotracheal intubation and IMV. On day 3 after admission, the puerpera regained consciousness, evacuated the IMV, and resumed enteral nutrition. She was then transferred to the maternity ward 24 h later. On day 7 after admission, the woman recovered and was discharged without any sequelae. CONCLUSION: MetHb can cross through the placental barrier. Level of MetHb both reflects severity of the sodium nitrite poisoning and serves as feedback on therapeutic effectiveness.

4.
Eye Contact Lens ; 2024 Aug 08.
Artículo en Inglés | MEDLINE | ID: mdl-39133174

RESUMEN

OBJECTIVES: The aim of this study was to analyze the effects of lens deviation on peripheral defocus and optic quality in adolescents with moderate and severe myopia. METHODS: This prospective study enrolled 81 children (81 eyes). The spherical equivalent was -5.0≤SE≤-6.0 diopter. The participants were divided into two subgroups based on their eccentricity (inferior temporal) after wearing the lenses for 12 months. Between them, the low eccentric subgroup (A) had a total eccentric distance of less than 0.5 mm, and the moderate and severe eccentric subgroup (B) had a total eccentric distance of ≥0.5 mm. Peripheral defocus and eccentricity were measured before and after wearing the lenses, and the Spearman test was used to compare the parameters. RESULTS: Parameters such as the total peripheral defocus (TRDV) were significantly lower in subgroup B than in subgroup A after 12 months of orthokeratology lens usage. The axial length growth (ΔAL) in subgroup A was higher than that in subgroup B. Axial length growth, TRDV, and other parameters were significantly associated with eccentricity. The modulation transfer function cutoff and Strehl ratio were also significantly associated with eccentricity. CONCLUSIONS: Greater eccentricity within a certain range can induce greater periretinal defocus and improve the ΔAL.

5.
Transl Oncol ; 48: 102074, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39106551

RESUMEN

Patients with EGFR-mutated non-small cell lung cancer (NSCLC) respond poorly to immune checkpoint inhibitors (ICIs). It has been reported that the number of CD8+T cells is reduced in EGFR-mutated NSCLC. However, the extent of heterogeneity and effector function of distinct populations of CD8+T cells has not been investigated intensively. In addition, studies investigating whether a combination of radiotherapy and ICIs can improve the efficacy of ICIs in EGFR-mutated lung cancer are lacking. Single-cell RNA sequencing (scRNA-seq) was used to investigate the heterogeneity of CD8+T cell populations in EGFR-mutated NSCLC. The STING pathway was explored after hypofractionated radiation of EGFR-mutated and wild-type cells. Mice bearing LLC-19del and LLC-EGFR tumors were treated with radiotherapy plus anti-PD-L1. The scRNA-seq data showed the percentage of progenitor exhausted CD8+T cells was lower in EGFR-mutated NSCLC. In addition, CD8+T cells in EGFR-mutated NSCLC were enriched in oxidative phosphorylation. In EGFR-mutated and wild-type cells, 8 Gy × 3 increased the expression of chemokines that recruit T cells and activate the cGAS-STING pathway. In the LLC-19del and LLC-EGFR mouse model, the combination of radiation and anti-PD-L1 significantly inhibited the growth of abscopal tumors. The enhanced abscopal effect was associated with systemic CD8+T cell infiltration. This study provided an intensive understanding of the heterogeneity and effector functions of CD8+T cells in EGFR-mutated NSCLC. We showed that the combination of hypofractionated radiation and anti-PD-L1 significantly enhanced the abscopal responses in both EGFR-mutated and wild-type lung cancer by activating CD8+T cells in mice.

6.
Adv Sci (Weinh) ; : e2406936, 2024 Aug 13.
Artículo en Inglés | MEDLINE | ID: mdl-39136142

RESUMEN

Despite significant progress in therapy, there remains a lack of substantial evidence regarding the molecular factors that lead to renal fibrosis. Neuraminidase 4 (NEU4), an enzyme that removes sialic acids from glycoconjugates, has an unclear role in chronic progressive fibrosis. Here, this study finds that NEU4 expression is markedly upregulated in mouse fibrotic kidneys induced by folic acid or unilateral ureter obstruction, and this elevation is observed in patients with renal fibrosis. NEU4 knockdown specifically in the kidney attenuates the epithelial-to-mesenchymal transition, reduces the production of pro-fibrotic cytokines, and decreases cellular senescence in male mice. Conversely, NEU4 overexpression exacerbates the progression of renal fibrosis. Mechanistically, NEU4254-388aa interacts with Yes-associated protein (YAP) at WW2 domain (231-263aa), promoting its nucleus translocation and activation of target genes, thereby contributing to renal fibrosis. 3,5,6,7,8,3',4'-Heptamethoxyflavone, a natural compound, is identified as a novel NEU4 inhibitor, effectively protecting mice from renal fibrosis in a NEU4-dependent manner. Collectively, the findings suggest that NEU4 may represent a promising therapeutic target for kidney fibrosis.

7.
J Med Chem ; 2024 Aug 13.
Artículo en Inglés | MEDLINE | ID: mdl-39136241

RESUMEN

The serine/threonine phosphatase family is important in tumor progression and survival. Due to the high conserved catalytic domain, designing selective inhibitors is challenging. Herein, we obtained compound 28a with 38-fold enhanced PP5 selectivity (PP2A/5 IC50 = 33.8/0.9 µM) and improved drug-like properties (favorable stability and safety, F = 82.0%) by rational drug design based on a phase II PP2A/5 dual target inhibitor LB-100. Importantly, we found the spatial conformational restriction of the 28a indole fragment was responsible for the selectivity of PP5. Thus, 28a activated p53 and downregulated cyclin D1 and MGMT, which showed potency in cell cycle arrest and reverse temozolomide (TMZ) resistance in the U87 MG cell line. Furthermore, oral administration of 28a and TMZ was well tolerated to effectively inhibit tumor growth (TGI = 87.7%) in the xenograft model. Collectively, these results implicate 28a could be a drug candidate by reversing TMZ resistance with a selective PP5 inhibition manner.

8.
iScience ; 27(8): 110454, 2024 Aug 16.
Artículo en Inglés | MEDLINE | ID: mdl-39104418

RESUMEN

Wnts are lipid-modified glycoproteins that play key roles in both embryonic development and adult homeostasis. Wnt signaling is dysregulated in many cancers and preclinical data shows that targeting Wnt biosynthesis and secretion can be effective in Wnt-addicted cancers. An integral membrane protein known as Wntless (WLS/Evi) is essential for Wnt secretion. However, WLS remains undrugged thus far. The cryo-EM structure of WLS in complex with WNT8A shows that WLS has a druggable G-protein coupled receptor (GPCR) domain. Using Active Learning/Glide, we performed an ultra-large scale virtual screening from Enamine's REAL 350/3 Lead-Like library containing nearly 500 million compounds. 68 hits were examined after on-demand synthesis in cell-based Wnt reporter and other functional assays. ETC-451 emerged as a potential first-in-class WLS inhibitor. ETC-451 blocked WLS-WNT3A interaction and decreased Wnt-addicted pancreatic cancer cell line proliferation. The current hit provides a starting chemical scaffold for further structure or ligand-based drug discovery targeting WLS.

9.
Zhongguo Zhong Yao Za Zhi ; 49(14): 3706-3713, 2024 Jul.
Artículo en Chino | MEDLINE | ID: mdl-39099345

RESUMEN

Acupoint drug delivery is a traditional external therapy of traditional Chinese medicine(TCM). Guided by the meridian and collateral theory in TCM, it applies medications to the skin at acupoints, exerting a dual therapeutic effect by stimulating the acupoints and the conduction of meridians. Acupoint drug delivery is widely used in clinical practice. Different from traditional oral admi-nistration and injection, it absorbs medications through the skin, effectively avoiding the first-pass effect of drugs and the toxic side effects caused by injection. Acupoint selection and transdermal drug absorption are pivotal factors affecting the efficacy of acupoint drug delivery. Recent research on acupoint drug delivery mainly focuses on the evaluation of clinical efficacy, yet the systematic investigations on acupoint selection and pharmacodynamic factors are scarce. This study reviews the mechanism, efficacy evaluation and application status of acupoint drug delivery. It integrates the theory of TCM with modern medicine to explore the mechanism of acupoint drug delivery, evaluate its clinical efficacy, and assess the transdermal penetration in vivo and in vitro. The application status of acupoint drug delivery is also summarized, including the selection of acupoints, application dosage form, application time and the absorption of acupoints. This review aims to offer insights and references for the research, development and clinical application of acupoint drug delivery products.


Asunto(s)
Puntos de Acupuntura , Sistemas de Liberación de Medicamentos , Humanos , Sistemas de Liberación de Medicamentos/métodos , Animales , Medicamentos Herbarios Chinos/administración & dosificación , Medicamentos Herbarios Chinos/farmacocinética , Absorción Cutánea/efectos de los fármacos , Meridianos , Medicina Tradicional China , Administración Cutánea
10.
Turk J Gastroenterol ; 35(6): 497-504, 2024 02 29.
Artículo en Inglés | MEDLINE | ID: mdl-39101697

RESUMEN

Background/Aims: Recent studies revealed that patients with persistent aminotransferase elevations after antiviral treatment had higher risk of hepatic events; yet its underlying causes remain unclear. Our study aimed to investigate the etiologies of persistent aminotransferase elevations in patients treated with nucleos(t)ide analogs (NAs). Materials and Methods: A retrospective study was conducted on chronic hepatitis B (CHB) patients who had been receiving NA treatment for over a year and had an aminotransferase level greater than 40 IU/mL (more than twice, with a 3-month interval) and subsequently underwent a liver biopsy. Results: The study group included 46 patients (34 males) with a mean age of 44.8 ± 20.3 years (range: 24-71 years).The average dura- tion of NA therapy was 3.7 years (1.1-10.6 years). The etiologies of persistant transaminase elevation were categorized into 4 groups: patients with low hepatitis B virus (HBV) viral load (LVL, n = 11); concurrent non-alcoholic fatty liver disease (NAFLD, n = 12); concurrent other liver diseases (OLD, n = 12); and unknown liver dysfunction (ULD, n = 11). The proportion of G ≥ 2 inflammation was significantly higher in the LVL group (90.9%) compared to NAFLD (33.3%), OLD (50%), and ULD (27.2%) groups (P = .012). The hepatitis B e-antigen (HBeAg)-positive group exhibited a younger age (34.5 ± 10.2 vs. 48.1 ± 9.4 years, P < .001), a lower proportion of fibrosis F ≥ 2 (36.3% vs. 77.1%, P = .012), and a higher prevalence of detectable HBV DNA (54.5% vs.14.2%, P = .00632) compared to the HBeAg-negative group. Conclusion: The etiology of persistent aminotransferase elevations in CHB patients undergoing NAs treatment warrants investigation. Besides the commonly observed NAFLD and low HBV viral load, concurrent presence of other liver diseases requires elucidation.The proportion of G≥2 inflammation was higher in the LVL group.


Asunto(s)
Alanina Transaminasa , Antivirales , Hepatitis B Crónica , Carga Viral , Humanos , Masculino , Hepatitis B Crónica/tratamiento farmacológico , Hepatitis B Crónica/complicaciones , Hepatitis B Crónica/sangre , Hepatitis B Crónica/virología , Femenino , Persona de Mediana Edad , Adulto , Estudios Retrospectivos , Antivirales/uso terapéutico , Antivirales/efectos adversos , Anciano , Adulto Joven , Alanina Transaminasa/sangre , Virus de la Hepatitis B , Hígado/patología , Enfermedad del Hígado Graso no Alcohólico , Nucleósidos/uso terapéutico
11.
PLoS One ; 19(8): e0308570, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39116157

RESUMEN

BACKGROUND: Tumor burden score (TBS) based on maximum tumor diameter and number has been shown to correlate with prognosis in patients with hepatocellular carcinoma (HCC). Nevertheless, the results are conflicting. Hence, we conducted a meta-analysis to analyze the association between TBS and survival outcomes of HCC patients. METHODS: A comprehensively search of the databases including PubMed, Embase and Web of Science was performed to retrieve studies satisfying the inclusion criteria until August 31, 2023. The hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated. All the data analyses were carried out by STATA 12.0. RESULTS: 10 retrospective studies containing 25073 patients were incorporated in the study. The results demonstrated that high TBS was markedly association with poor overall survival (OS) (HR: 1.79, 95% CI: 1.45-2.23) and relapse-free survival / progression-free survival(RFS/PFS) (HR: 1.71; 95% CI: 1.42-2.07). Subgroup analysis showed that the prognostic value of TBS in HCC was not affected by any subgroup. CONCLUSIONS: TBS may be an efficient prognostic index in HCC patients.


Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , Carga Tumoral , Carcinoma Hepatocelular/mortalidad , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/diagnóstico , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/patología , Humanos , Pronóstico , Estudios Retrospectivos
12.
Artículo en Inglés | MEDLINE | ID: mdl-39113679

RESUMEN

Purpose: To describe the anatomical and histological characteristics of the human MTL (meniscotibial ligament) that keeps the meniscus stable and are rarely discussed. Study design: Descriptive laboratory study. Methods: In total, six fresh-frozen adult cadaver knees were dissected, and the dissection protocol were designed by two experienced anatomy professors. The anatomical morphology of MTL was observed. The main anatomical specimens included meniscus, tibial plateau, MTL. The osteotome was used to excise the portion of the tibial plateau, which could obtain the complex including partial meniscus, MTL, and a tibial fragment. A histopathologic study was performed by two experienced pathologists. Results: Macroscopically, the MTL could be divided into two parts: medial meniscotibial ligament (MMTL)and lateral meniscotibial ligament (LMTL). The MMTL is distributed continuously, whereas the LMTL is discontinuous on the tibial plateau. The average length from the tibial attachment of the LMTL to the articular surface was 19 ± 1.0mm (mean ± SD). The average length from the tibial attachment of the MMTL to the articular surface was 10 ± 1.2 mm (mean ± SD). Microscopy of the MTL showed that the MTL is a ligamentous tissue, composed of a network of oriented collagenous fibers. Conclusions: In all knees, the MTL was inserted on the outer edge of the meniscus, attaching to the tibia below the level of articular cartilage, which was key to maintaining the rotational stability of knee and the meniscus in the physiological position on the tibial plateau. Histological analysis of this ligament demonstrated that the MTL is a veritable ligamentous structure, which is made up of collagen type I-expressing fibroblasts. Clinical relevance: This article contributes to the understanding of the anatomical and histological characteristics of the MTL. It is beneficial to promote the development of relevant surgical techniques for the MTL lesion.

13.
Fish Shellfish Immunol ; 153: 109821, 2024 Aug 06.
Artículo en Inglés | MEDLINE | ID: mdl-39117129

RESUMEN

Polymeric immunoglobulin receptor (pIgR) is an important immune factor in the mucosal immune system of fish, which plays a key role in mediating the secretion and transport of immunoglobulin into mucus. In this study, the full-length cDNA sequence of Megalobrama amblycephala pIgR gene was firstly cloned and the immune response to Aeromonas hydrophila was detected. After being challenged by Aeromonas hydrophila at 3 d, significantly pathological features were observed in intestine, head kidney, spleen, liver and gill of Megalobrama amblycephala. The content of lysozyme (Lys) and the activities of acid phosphatase (ACP) and alkaline phosphatase (AKP) increased significantly at 1 d and reached the peak at 3 d, and the activities of total superoxide dismutase (T-SOD), glutathione peroxidase (GSH-PX) and catalase (CAT) in serum reached the peak at 5 d and 7 d after infection, respectively. The expression level of IL-1ß gene reached the peak at 3 d in intestine, 5 d in gill and spleen, 7 d in head kidney and liver of Megalobrama amblycephala after infected by Aeromonas hydrophila, respectively. The TNF-α gene expression reached the peak at 3 d in intestine and gill, 5 d in head kidney and spleen, 7 d in liver after infection, respectively. The experimental results showed that the infection of Aeromonas hydrophila caused the pathological changes of immune-related tissues and triggered the inflammation responses. The full-length cDNA sequence of Megalobrama amblycephala pIgR was 1828 bp, and its open reading frame (ORF) was 1023 bp, encoding 340 amino acids. The pIgR of Megalobrama amblycephala has a signal peptide sequence, followed by extracellular region, transmembrane region and intracellular region. The extracellular region includes two Ig-like domains (ILDs), and its tertiary structure is twisted "L". The phylogenetic tree was constructed using the adjacency method, and the pIgR genes of Megalobrama amblycephala and cyprinidae fish were clustered into a single branch. Quantitative real-time PCR (qRT-PCR) was used to detect the expression of pIgR gene in different tissues of Megalobrama amblycephala. The expression level of pIgR gene was the highest in liver, followed by intestine, head kidney, skin, middle kidney and spleen, lower in heart, gill and brain, and the lowest in muscle. After being infected by Aeromonas hydrophila, the expression level of Megalobrama amblycephala pIgR gene in intestine, head kidney, spleen, liver and gill showed a trend of increasing first and then decreasing within 28 d. The pIgR gene expression reached the peak in mucosal immune-related tissues (gill and intestine) was earlier than that in systemic immune-related tissues (head kidney and spleen), and the relative expression level of pIgR gene at peak in intestine (12.3 fold) was higher than that in head kidney (3.73 fold) and spleen (7.84 fold). These results suggested that Megalobrama amblycephala pIgR might play an important role in the mucosal immune system to against Aeromonas hydrophila infection.

14.
Mol Divers ; 2024 Aug 09.
Artículo en Inglés | MEDLINE | ID: mdl-39117890

RESUMEN

Given the critical necessity for the development of more potent anti-cancer drugs, a series of novel compounds incorporating trifluoromethyl groups within the privileged 2-anilinoquinoline scaffold was designed, synthesized, and subjected to biological evaluation through a pharmacophore hybridization strategy. Upon evaluating the in vitro anti-cancer characteristics of the target compounds, it became clear that compound 8b, which contains a (4-(piperazin-1-yl)phenyl)amino substitution at the 2-position of the quinoline skeleton, displayed superior efficacy against four cancer cell lines by inducing apoptosis and cell cycle arrest. Following research conducted in a PC3 xenograft mouse model, it was found that compound 8b exhibited significant anti-cancer efficacy while demonstrating minimal toxicity. Additionally, the analysis of a 217-kinase panel pinpointed SGK1 as a potential target for this compound class with anti-cancer capabilities. This finding was further verified through molecular docking analysis and cellular thermal shift assays. To conclude, our results emphasize that compound 8b can be used as a lead compound for the development of anti-cancer drugs that target SGK1.

15.
J Med Chem ; 2024 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-39145509

RESUMEN

The activation of PP5 is essential for a variety of cellular processes, as it participates in a variety of biological pathways by dephosphorylating substrates. However, activation of PP5 by small molecules has been a challenge due to its native "self-inhibition" mechanism, which is controlled by the N-terminal TPR domain and the C-terminal αJ helix. Here, we reported the discovery of DDO-3733, a well-identified TPR-independent PP5 allosteric activator, which facilitates the dephosphorylation process of downstream substrates. Considering the negative regulatory effect of PP5 on heat shock transcription factor HSF1, pharmacologic activation of PP5 by DDO-3733 was found to reduce the HSP90 inhibitor-induced heat shock response. These results provide a chemical tool to advance the exploration of PP5 as a potential therapeutic target and highlight the value of pharmacological activation of PP5 to reduce heat shock toxicity of HSP90 inhibitors.

16.
J Oral Rehabil ; 2024 Aug 05.
Artículo en Inglés | MEDLINE | ID: mdl-39101668

RESUMEN

BACKGROUND: Syndecan 4 (SDC4), a type I transmembrane proteoglycan, serves as a critical link between chondrocytes and the extracellular matrix. OBJECTIVE: This study aimed to explore the role of SDC4 in cartilage degeneration of temporomandibular joint osteoathritis (TMJOA). METHODS: Condylar chondrocytes were stimulated with varying concentrations of recombinant rat interleukin-1ß (rrIL-1ß) and SDC4 small interfering RNA (si-SDC4). Anti-SDC4 ectodomain-specific antibodies or IgG were intra-articularly administrated in a TMJOA model rats. SDC4 conditional knockout (SDC4-cKO) and Sdc4flox/flox mice were induced TMJOA. Cartilage degeneration was assessed using haematoxylin & eosin (H&E) and safranin O (SO) staining. Protein levels of SDC4, matrix metalloproteinases (MMPs), a disintegrin and metalloproteinase with a thrombospondin motifs 5 (ADAMTS5), tumour necrosis factor α (TNFα), type II collagen (Col-II), aggrecan (ACAN), cleaved caspase 3 (CASP3), Ki67 and related pathways in condylar cartilage were evaluated by immunohistochemical (IHC) staining or western blot assays. RESULTS: SDC4 expression was evidently increased in MIA-model animals compared to control groups. rrIL-1ß stimulation increased the expression of SDC4, MMP3 and ADAMTS5 expression in chondrocytes, while decreasing the expression of Col-II. These effects were reversed by si-SDC4 in vitro. In vivo, SDC4 blockade reduced the death of chondrocytes and the loss of cartilage matrix, which was evidenced by increased expression of Col-II and ACAN, and a decrease in SDC4, MMP13 and cleaved-CASP3-positive cells. Furthermore, the protein levels of ACAN and Ki67 were elevated, and the ERK1/2 and P38 signalling pathways were activated following SDC4 inhibition. CONCLUSIONS: SDC4 inhibition significantly ameliorates condylar cartilage degeneration, which was mediated, at least partly, through P38 and ERK1/2 signalling. Inhibition of SDC4 may be of great value for the treatment of TMJOA.

17.
Nat Prod Res ; : 1-6, 2024 Jul 24.
Artículo en Inglés | MEDLINE | ID: mdl-39049541

RESUMEN

The aim of this study was to explore the uric acid-lowering effect and renal protective effect of Eucommia ulmoides leaf extract (EULE). The results of xanthine oxidase inhibition assay showed EULE exhibited a high inhibition rate similar to that of allopurinol, with an IC50 value of 1.53 mg/mL. A chronic kidney disease (CKD) model was established in adenine-induced rats to investigate the therapeutic effect of EULE on CKD. The results demonstrated EULE could reduce blood pressure and improve renal index. Additionally, EULE could regulate serum and urine indicators of renal function injury, and restore renal tissue morphology. Mechanistically, EULE was found to downregulate levels of malondialdehyde (MDA), tumour necrosis factor-α (TNF-α), and interleukin-1ß (IL-1ß), while upregulating total antioxidant capacity (T-AOC), thereby alleviating inflammatory response in rats, leading to a reduction in renal damage. the Our findings provide potential applications of EULE as a natural product for the improvement of renal injury.

18.
J Colloid Interface Sci ; 676: 859-870, 2024 Jul 14.
Artículo en Inglés | MEDLINE | ID: mdl-39067221

RESUMEN

The catalytic oxidation of formaldehyde (HCHO) at ambient temperature is a highly efficient, cost-effective and environmentally friendly approach for formaldehyde removal. Reactive oxygen (O*) and reactive hydroxyl groups (OH*) are the main active species in the catalytic oxidation reaction of HCHO. Therefore, it is crucial to design catalysts that can simultaneously enhance the surface concentrations of O* and OH*, thereby improving their overall catalytic performance. The present study aimed to design an Al2O3/CoNC catalyst featuring layered carbon nitride coupled with metal oxides possessing domain-limited cobalt (Co) metal active sites, to efficiently remove HCHO (≈100 %, 100 ppm, RH=50 %, GSHV=20,000 mL/(g h)) and ensure stability (more than 90 % formaldehyde removal within 450 h) at ambient temperature. The characterization revealed that the interaction between Al2O3-supported metal and CoNC resulted in enhanced confinement of Co, leading to a higher abundance of edge structures exposing more active sites. Additionally, the presence of highly dispersed Co-NX active sites and increased oxygen vacancies effectively facilitated the adsorption and activation processes of HCHO and O2, as well as the adsorption and desorption dynamics of intermediates during the reaction. These factors collectively contributed to an improved catalytic activity. The results of in situ infrared spectroscopy revealed that the catalyst improved the adsorption and activation of O2 and H2O, leading to the rapid generation of substantial amounts of O* and OH*. This synergistic interaction between Al2O3 and CoNC plays a crucial role in the sustained production of O* and OH*, promoting efficient of intermediate decomposition, and ensuring excellent catalytic activity and stability for HCHO.

19.
Inorg Chem ; 63(30): 14193-14199, 2024 Jul 29.
Artículo en Inglés | MEDLINE | ID: mdl-39021089

RESUMEN

The development of efficient and sustainable methods for reducing carbon dioxide (CO2) and converting it into valuable hydrocarbons has gained significant attention. In this study, researchers focused on Ti4+-doped metal-organic framework (MOF-74) photocatalysts. The incorporation of Ti4+ ions into the MOF-74 structure was achieved through a one-pot hydrothermal method. By replacing Zn2+ ions with Ti4+ ions in a substitutional manner, researchers have aimed to enhance the photocatalytic activity of the CO2 reduction. The obtained Ti4+-doped MOF-74 photocatalysts exhibited a significantly improved performance in the reduction of CO2 into carbon monoxide (CO). The doping of Ti4+ ions induced energy bands below the conduction band minimum (CBM) of MOF-74, extending the visible response range and enabling the photocatalysts to utilize a broader spectrum of light for catalytic reactions. This extension of the visible response range enables photocatalysts to utilize a broader spectrum of light for catalytic reactions. The incorporation of Ti4+ ions not only extends the visible response range but also suppresses charge carrier recombination. This work provides valuable insights into the design principles of MOF-based photocatalysts and paves the way for their practical implementation in addressing the energy crisis and reducing greenhouse gas emissions.

20.
Front Oncol ; 14: 1383523, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39055551

RESUMEN

Backgroud: In recent years, as the number of people with obesity has surged, the number of morbidly obese patients has also grown. The pathophysiological changes in morbid obesity can lead to combined lung diseases, which may result in hypoventilation, hypoxemia, acute upper airway obstruction, acute respiratory distress syndrome, and sleep apnea syndrome, posing serious challenges to anesthesia management. Here, we describe a case of the administration of remimazolam combined with remifentanil in a patient with morbid obesity undergoing gastroscopy. This has rarely been reported in clinical practice, and we present our management experience here with the aim of providing a reference for clinical work. Case presentation: We report the case of a 32-year-old male hypertensive patient with a height of 180 cm, weight of 145 kg, and body mass index of 44.8 kg/m2. The patient's main complaint was intermittent hunger pain for more than 1 year, and duodenal polyps were found. Considering the patient's morbid obesity and the combination of sleep apnea syndrome and hypertension, we administered remimazolam along with remifentanil to ensure perioperative safety. Conclusion: The procedure lasted 30 min, and the anesthesia was satisfactory with no complications. Remimazolam combined with remifentanil intravenous anesthesia is safe for short gastroscopy in patients with morbidly obesity. The administration of a small dose of split-titration delivery facilitates the maintenance of stable vital signs.

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